[Fat Bear Science] Cancer gene testing | Oncologists summarize 10 issues that people are particularly concerned about in clinical practice

With the aging of the population and the occurrence of environmental pollution, the incidence of malignant tumors is on the rise and has become the second leading cause of death after cardiovascular and cerebrovascular accidents. From the perspective of the pathogenesis of cancer, the most fundamental mechanism is that under the influence of internal and external factors, the genes of some cells in the human body change and become malignant tumors. Angelina Jolie, a well-known international movie star, had a preventive double mastectomy in May 2013 to reduce the risk of breast cancer.

Hollywood actress Angelina Jolie

Jolie had her breasts removed because she found out through testing that the BRCA1 gene in her body had changed, and this gene change can lead to an 87% and 50% chance of developing breast cancer and ovarian cancer, respectively. So in order to prevent breast cancer, she chose to have her breasts removed. So, today, let's talk about cancer gene testing.

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Yu Huiqing

Director of the Department of Palliative Medicine/Nutrition, Chongqing University Cancer Hospital, chief physician, and master's supervisor.

He is good at the diagnosis and treatment of diseases such as lung cancer, colorectal cancer, gastric cancer, tumor chemotherapy, molecular targeted therapy, biological immunotherapy, cancer pain, tumor nutrition, etc.

Clinic hours: Monday morning, Wednesday morning

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Wang Sixiong

Associate Chief Physician, Doctor of Medicine.

He specializes in the diagnosis and treatment of malignant tumors such as lung cancer, colorectal cancer, liver cancer, gastric cancer, esophageal cancer, sarcoma, etc. He is also good at chemotherapy, targeted therapy, immunotherapy and standardized diagnosis and treatment of cancer pain for malignant tumors.

Tumor clinic hours: Thursday afternoon and Friday afternoon

What are genes and susceptibility genes?

01

We know that there are 23 pairs of chromosomes in the human body, one in each pair comes from the father and the other from the mother. The genes on these 23 pairs of chromosomes determine a person's appearance, height, physical fitness and susceptibility to disease (i.e. the severity of the disease). In the same living environment, for example, workers in shoe factories are often exposed to chemicals such as benzene, but some people get bladder cancer because of this, but some people do not get this cancer. This shows that people who get bladder cancer have changes in their genes (medically called gene mutations, susceptibility genes), and the body cannot metabolize and remove harmful substances such as benzene, so these people are more likely to get cancer.

Which groups of people need tumor gene testing?

02

Most tumors are caused by acquired genetic changes and are sporadic. They occur under the influence of various factors such as the body's internal and external environment. We can reduce the risk of cancer through a healthy lifestyle, proper exercise, quitting smoking and drinking, controlling weight, balanced nutrition, and vaccination.

However, a small number of tumors are related to genetics, that is, the cancer susceptibility genes carried by parents are passed on to their offspring. For example, familial adenomatous polyposis of the colon can be passed from parents to children, leading to an increased risk of colon cancer.

For example, the latest data shows that the incidence of breast cancer has surpassed lung cancer to become the number one tumor. People who carry BRCA1 and BRCA2 gene mutations have an 80% chance of developing breast cancer in their lifetime. Offspring whose mothers have breast cancer or ovarian cancer may have BRCA1 and BRCA2 gene mutations, which increases the risk of breast cancer and ovarian cancer. So do healthy people who have relatives with breast cancer need to undergo BRCA1 and BRCA2 gene testing? The answer is no. Experts recommend that if two first-degree relatives (such as sisters, mother and daughter) have unilateral breast cancer or ovarian cancer, or if one has bilateral breast cancer, BRCA1 and BRCA2 gene testing can be considered to predict the risk of breast cancer and ovarian cancer.

If a breast cancer gene mutation is detected, is a mastectomy necessary?

03

For those with the above-mentioned family history of breast cancer, if BRCA1 and BRCA2 gene changes are detected, these women need to choose whether to undergo mastectomy under the guidance of a doctor and based on their own wishes, because the surgery is to remove the breast tissue visible to the naked eye, and there may be tiny breast tissue residues. These residual breast tissues may also become cancerous, but the risk of breast cancer is greatly reduced after the surgery. This preventive surgery is different from the mastectomy for breast cancer patients. It often removes breast tissue that may become cancerous and tries to preserve other breast structures without affecting the appearance. For those who resist surgery, they can have regular breast examinations to detect tumors early and remove them early. At the same time, they can take some oral medications to prevent the occurrence of breast cancer.

Jolie and Pitt's daughter

Do all cancer patients need to undergo genetic testing?

04

Earlier we talked about genetic testing for tumors in healthy people. For patients who already have cancer, the purpose of genetic testing is mainly to treat the tumor, which is the very popular targeted and immunotherapy today. Broadly speaking, all cancer patients can undergo genetic testing, but different genetic tests are suitable for different tumors, different stages and different patients.

For example, for advanced non-small cell lung cancer, there are many types of targeted drugs, including first-generation, second-generation and third-generation targeted drugs. At this time, we need to conduct genetic testing, such as EGFR, ALK and ROS1, etc. Different targeted drugs are selected for different mutations. This is the precision treatment of tumors.

Do all targeted drugs require genetic testing?

05

The answer is no. For some targeted drugs against tumor angiogenesis, genetic testing is not required, such as anlotinib and bevacizumab for advanced non-small cell lung cancer, sorafenib and lenvatinib for hepatocellular carcinoma, regorafenib and furiquintinib for colon cancer, etc. Because these drugs have many targets, it is not clear which tumor gene mutations are related to the efficacy of the drugs.

Will targeted drugs be available after genetic testing?

06

No, because there are too many types of gene mutations. For most gene mutations, it cannot be determined whether they are related to tumors. There are some tumor-related genes such as KRAS and TP53, for which there are currently no targeted drugs available. Therefore, patients are faced with a thick genetic testing report like a magazine, which may list dozens of mutated genes, but there are no suitable targeted drugs available for these genes.

If there is no gene mutation, is there no targeted drug available?

07

As mentioned above, some targeted drugs against tumor blood vessels can be used without drug gene testing. For patients without sensitive gene mutations, such as advanced non-small cell lung cancer (such as lung adenocarcinoma), the efficacy of chemotherapy combined with immunotherapy or bevacizumab treatment may not be worse than that of patients with mutations.

When do cancer patients need to undergo genetic testing again?

08

After using targeted drugs for a certain period of time, patients will develop drug resistance and their condition will progress. At this time, genetic testing can be performed again. For example, patients with advanced non-small cell lung cancer with EGFR sensitive mutations will progress after using targeted drugs such as gefitinib and icotinib for a period of time. At this time, genetic testing is performed again. Some patients may have new gene mutations (T790M positive mutations), and this T790M positive mutation can be treated with third-generation targeted drugs such as osimertinib or ametinib to control tumors and prolong patient survival.

What kind of specimens are best for genetic testing?

09

Genetic testing is best performed with specimens rich in tumor tissue. Generally speaking, surgical biopsy specimens are preferred, preferably recent surgical specimens, because they best represent the genetic status of the patient's current tumor.

Secondly, surgical specimens taken within 1 year can be selected.

Third, pleural effusion and ascites can be selected for testing. The more cancer cells are shed in the pleural effusion and ascites, the more reliable the test will be.

Fourth, for patients with recurrence and metastasis, if the risk of another surgical biopsy is high or it is difficult to obtain specimens, blood genetic testing can be selected. However, it should be noted that the number of cancer cells in the blood circulation may be small. If the genetic test is negative, it is not necessarily true gene negative. It may be because there are fewer cancer cells. The blood can be rechecked multiple times (such as once every 3 months).

How to choose tumor gene testing?

10

Different tumors require different targeted drugs. If a lot of genes are tested but no targeted drugs are available, it will waste both precious specimens and treatment funds. Therefore, patients should communicate with their doctors during tumor diagnosis and treatment, especially when the tumor is first diagnosed, and choose different genetic testing options based on the tumor stage and tumor type, in order to obtain evidence for the use of corresponding targeted drugs.

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